Turnover of myelin and other structural proteins in the developing rat brain

Sabri, Mohammad I.; Bone, A. H.; Davison, Alan

doi:10.1042/bj1420499

Cited by 66 publications

(56 citation statements)

References 23 publications

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“…This may reflect either a differential reduction in the transcription rate or in the stability of the messages for the two proteins. Interestingly, this difference in mRNA levels correlates well with reports that MBP turns over more rapidly than PLP (31,32).…”

Section: Discussionsupporting

confidence: 87%

Study of the expression of myelin proteolipid protein (lipophilin) using a cloned complementary DNA

et al. 1985

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We have prepared a XgtlO cDNA library with the mRNA isolated from fetal calf brains which were actively myelinating. Using two oligonucleotides made according to the known amino acid sequence of myelin proteolipid protein (PLP or lipophilin), we have isolated several cDNA clones for this major intrinsic membrane protein of myelin. One of these clones, designated as pLPl, is found to contain 444 bp of coding sequence for the C-terminal half of PLP and 486 bp of 3' untranslated sequence. Using pLPl as a hybridization probe, we have studied the regulation of PLP at the mRNA level during rat brain development. Our results show that the relative amounts of mRNA for PLP and that for the major extrinsic protein of the myelin membrane, myelin basic protein, increase coordinately during the course of myelination in the brain.

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Section: Discussionsupporting

confidence: 87%

Study of the expression of myelin proteolipid protein (lipophilin) using a cloned complementary DNA

et al. 1985

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“…These include the rapid downregulation of myelin genes PLP and MAG at 1 week after 4OHT (before any detectable loss of recombined cells and when the recombined MRF allele was still being expressed at control levels), the gradual loss of markers usually associated with myeli- nating cells (such as CC1 and CNP) and the observation that the processes of the surviving eYFP ϩ iCKO cells at 8 weeks after 4OHT generally no longer appeared to be associated with intact myelin sheaths. Compacted myelin in vivo is thought to be a remarkably stable structure (for review, see Aggarwal et al, 2011); both the protein (Sabri et al, 1974) and lipid (Saher and Simons, 2010) components of myelin can have half-lives of months in vivo. Despite this stability, the components of myelin would appear to show some degree of turnover, and it seems likely that the dysregulation of myelin genes, such as PLP and MAG, ultimately leads to a loss of the ability of the cells to maintain their myelin sheaths independent of their survival.…”

Section: Discussionmentioning

confidence: 99%

Myelin Gene Regulatory Factor Is Required for Maintenance of Myelin and Mature Oligodendrocyte Identity in the Adult CNS

et al. 2012

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Although the transcription factors required for the generation of oligodendrocytes and CNS myelination during development have been relatively well established, it is not known whether continued expression of the same factors is required for the maintenance of myelin in the adult. Here, we use an inducible conditional knock-out strategy to investigate whether continued oligodendrocyte expression of the recently identified transcription factor myelin gene regulatory factor (MRF) is required to maintain the integrity of myelin in the adult CNS. Genetic ablation of MRF in mature oligodendrocytes within the adult CNS resulted in a delayed but severe CNS demyelination, with clinical symptoms beginning at 5 weeks and peaking at 8 weeks after ablation of MRF. This demyelination was accompanied by microglial/macrophage infiltration and axonal damage. Transcripts for myelin genes, such as proteolipid protein, MAG, MBP, and myelin oligodendrocyte glycoprotein, were rapidly downregulated after ablation of MRF, indicating an ongoing requirement for MRF in the expression of these genes. Subsequently, a proportion of the recombined oligodendrocytes undergo apoptosis over a period of weeks. Surviving oligodendrocytes gradually lose the expression of mature markers such as CC1 antigen and their association with myelin, without reexpressing oligodendrocyte progenitor markers or reentering the cell cycle. These results demonstrate that ongoing expression of MRF within the adult CNS is critical to maintain mature oligodendrocyte identity and the integrity of CNS myelin.

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“…This is true despite the fact that 14 out of the 31 amino acids have at least four degenerate codons and that 6 have six degenerate codons involving changes in two positions of the triplet codon. That a variety of mRNAs were selected by hybridization to immobilized pNZ111 is also indicated by the RNA blot analysis of brain mRNA (Fig.…”

mentioning

confidence: 88%

“…The myelin basic protein (MBP) constitutes about 33% of the protein of the myelin sheath in the central nervous system and 1-10% in the peripheral (6,7). In most species, the predominant form of the MBP has a molecular mass of 18.5 kilodaltons (kDa), and the primary sequence of this protein is well conserved in animals as distantly related as the chicken, human, and rat (8)(9)(10).…”

mentioning

confidence: 99%

Characterization of mouse myelin basic protein messenger RNAs with a myelin basic protein cDNA clone.

Zeller¹,

Hunkeler²,

Campagnoni³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

116

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Using a family of synthetic tetradecamer oligonucleotides as a primer for cDNA synthesis and a second family of tetradecamers as a hybridization probe, we have prepared and isolated a cDNA clone of mouse myelin basic protein (MBP). The clone, pNZ111, corresponds to the region of the mRNA that codes for an amino acid sequence present in all four major forms of MBP (2)(3)(4)(5). Large amounts of the membrane are produced relative to the size of the myelin-forming cell. The process involves the synthesis of myelin-specific proteins followed by their integration into the growing membrane. During early myelinogenesis, membranes are formed that are loosely whorled around the axon. As myelin maturation proceeds, compaction of these membranes occurs to form the tight multilamellar structure characteristic of myelin.The myelin basic protein (MBP) constitutes about 33% of the protein of the myelin sheath in the central nervous system and 1-10% in the peripheral (6, 7). In most species, the predominant form of the MBP has a molecular mass of 18.5 kilodaltons (kDa), and the primary sequence of this protein is well conserved in animals as distantly related as the chicken, human, and rat (8-10). Two major forms of MBP predominate in rats and mice: one of these corresponds to the single major protein found in other species (18.5 kDa) and the other has a molecular mass of 14 kDa. In rats, the 14-kDa MBP is identical in sequence to the 18.5-kDa MBP, except for an internal deletion of residues 118-158 [numbered according to Martenson (11)] near the carboxyl terminus of the protein (10, 12). Two quantitatively minor forms of MBP have been found in rats and mice-a 21.5-kDa protein that is presumably identical to the 18.5-kDa MBP, except for the inclusion of a 25-30 amino acid sequence in the NH2-terminal half of the molecule and a 17-kDa MBP that bears the same relationship to the 14-kDa MBP (13).Myelination occurs postnatally in mouse brain beginning 8-10 days postpartum and continuing actively for 7-10 wk, with the maximal rate of myelin deposition occurring at about 18 days (4). Maximal synthesis of the 18.5-kDa and 14-kDa MBPs occurs at 18 days in vivo and coincides closely with the peak of myelin synthesis (14). During myelin maturation in the mouse, the proportions of the four MBPs in the membrane change (15-17) and this may be due to alterations in the relative rates of synthesis of the four proteins with age. With maturation, the proportion of the two minor MBPs (i.e., the 21.5 kDa and 17 kDa in myelin falls relative to the 18.5-kDa proteins and the 14-kDa/18.5-kDa MBP ratio increases dramatically. This latter change has been correlated with the relative rate of synthesis of these two proteins in vivo (14). Recently, Carson et al. (18) have identified trace amounts of larger forms of MBP that appear during the early stages of myelination. Identification of these larger forms has depended on immunoreagents and the relationships of the amino acid sequences to the major MBPs have, as yet, not been determined.We have r...

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Turnover of myelin and other structural proteins in the developing rat brain

Cited by 66 publications

References 23 publications

Study of the expression of myelin proteolipid protein (lipophilin) using a cloned complementary DNA

Study of the expression of myelin proteolipid protein (lipophilin) using a cloned complementary DNA

Myelin Gene Regulatory Factor Is Required for Maintenance of Myelin and Mature Oligodendrocyte Identity in the Adult CNS

Characterization of mouse myelin basic protein messenger RNAs with a myelin basic protein cDNA clone.

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